Gene amplification during differentiation of mesenchymal stem cells towards chondrocytes
- 1Department of Human Genetics, Saarland University, D-66421 Homburg, Saarland, Germany
- 2Center of Experimental Orthopedics, Saarland University Medical Center, D-66421 Homburg, Saarland, Germany
- 3Chair of Clinical Bioinformatics, Saarland University, D-66123 Saarbrücken, Saarland, Germany
Abstract
For decades, gene amplification was described as an attribute of tumor cells and as a physiological mechanism to increase gene copy numbers for the higher protein demand during the development of amphibians and flies. Notably, gene amplification has since been detected in normal mammalian cells during differentiation. Numerous amplified genes detected in tumor cells overlap with amplified genes detected during stem cell differentiation. Since stem cells have a valuable potency in regenerative therapies and since cartilage regeneration is a highly demanded therapeutic strategy, the current study investigated gene amplification dynamics during the chondrogenic differentiation of human mesenchymal stem cells (hMSCs). Using quantitative PCR, copy number changes were analyzed for genes previously implicated in differentiation, as well as genes amplified in chondrosarcoma, including CDK4, MDM2, AGAP2, CPT1B, SHANK3, TRIB1 and MYC. Amplifications were transient and stage-specific: CDK4, CPT1B and SHANK3 exhibited the highest copy number increases at day 2, followed by a gradual decline by day 7, whereas AGAP2 and MDM2 increased later in differentiation. Laser microdissection of toluidine blue-stained areas revealed heterogeneity in amplification patterns: CDK4 amplification was prominent in areas lacking or showing moderate proteoglycan deposition; CPT1B amplification occurred in regions with absent, moderate or intense proteoglycan deposition; and SHANK3 amplification was restricted to areas with intense proteoglycan deposition. Notably, regions with the strongest proteoglycan staining exhibited no gene amplification, suggesting that gene amplification is an early, transient event that diminishes as differentiation progresses. These findings highlight gene amplification as a mechanism during chondrogenesis, potentially critical for early differentiation stages and genome stability in mature cells.
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BibTeX
@article{schwarz2026gene,
title = {{Gene amplification during differentiation of mesenchymal stem cells towards chondrocytes}},
author = {Paula E. Schwarz and Magali Cucchiarini and Shusruto Rishik and Andreas Keller and Eckart Meese and Ulrike Fischer},
journal = {Experimental and Therapeutic Medicine},
year = {2026},
month = oct,
doi = {10.3892/etm.2026.13341},
url = {https://europepmc.org/article/PMC/PMC13728488},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Gene amplification during differentiation of mesenchymal stem cells towards chondrocytes
AU - Paula E. Schwarz
AU - Magali Cucchiarini
AU - Shusruto Rishik
AU - Andreas Keller
AU - Eckart Meese
AU - Ulrike Fischer
PY - 2026
DA - 2026/10/23
JO - Experimental and Therapeutic Medicine
DO - 10.3892/etm.2026.13341
UR - https://europepmc.org/article/PMC/PMC13728488
AB - For decades, gene amplification was described as an attribute of tumor cells and as a physiological mechanism to increase gene copy numbers for the higher protein demand during the development of amphibians and flies. Notably, gene amplification has since been detected in normal mammalian cells during differentiation. Numerous amplified genes detected in tumor cells overlap with amplified genes detected during stem cell differentiation. Since stem cells have a valuable potency in regenerative therapies and since cartilage regeneration is a highly demanded therapeutic strategy, the current study investigated gene amplification dynamics during the chondrogenic differentiation of human mesenchymal stem cells (hMSCs). Using quantitative PCR, copy number changes were analyzed for genes previously implicated in differentiation, as well as genes amplified in chondrosarcoma, including CDK4, MDM2, AGAP2, CPT1B, SHANK3, TRIB1 and MYC. Amplifications were transient and stage-specific: CDK4, CPT1B and SHANK3 exhibited the highest copy number increases at day 2, followed by a gradual decline by day 7, whereas AGAP2 and MDM2 increased later in differentiation. Laser microdissection of toluidine blue-stained areas revealed heterogeneity in amplification patterns: CDK4 amplification was prominent in areas lacking or showing moderate proteoglycan deposition; CPT1B amplification occurred in regions with absent, moderate or intense proteoglycan deposition; and SHANK3 amplification was restricted to areas with intense proteoglycan deposition. Notably, regions with the strongest proteoglycan staining exhibited no gene amplification, suggesting that gene amplification is an early, transient event that diminishes as differentiation progresses. These findings highlight gene amplification as a mechanism during chondrogenesis, potentially critical for early differentiation stages and genome stability in mature cells.
SN - 1792-0981
SN - 1792-1015
ER -